[CIS PIDD] [cis-pidd] Newborn with positive for SCID

Thu Jan 15 01:48:18 EST 2015

Dear David,

*TBX1* seems most likely. Do his facial features fit with DGS/VCFS? It
would be worth asking the lab to manually check the array for *TBX1- *sometimes
the software may not call a small CNV if the probe density is low and many
NGS pipelines do not call CNVs.

Our cytogenetics lab (SA Pathology, South Australia) often have
difficulties with interpreting DEB breakage studies of white cells (cf.
radiation) in fetuses/infants, partly because of difficulties obtaining a
timely age-matched control, so we use Quest Diagnostics in New Jersey for
this age-group.

Kind regards,

Dylan
South Australian Clinical Genetics Service

Dylan Mordaunt
Mobile: + 61 468 516 283
Email: d.a.mordaunt at gmail.com

On 15 January 2015 at 16:47, David Buchbinder <dbuchbinder at choc.org> wrote:

>  Dear Colleagues -
>
> We have a 7 week old male with a history of a positive newborn screen for
> SCID.  He was born at 38 weeks and also noted to be IUGR with anomalies as
> noted above. He is an only child, parents are Egyptian and second cousins.
> The family history is unremarkable.
>
> Neuro:  A head US, brain MRI, and EEG are all normal.
>
> HEENT:  ear anomalies with pre-auricular ear tag.
>
> CV:  small muscular VSD,  CT angio with right-sided aortic arch with an
> aberrant left subclavian artery as well as a large patent ductus arteriosus
> resulting in a vascular ring.
>
> Resp:  no choanal atresia, but pharyngeal hypotonia noted
>
> GI:  imperforate anus, duodenal web (excised) – wound cellulitis treated
> with antibiotics (complicated by drug associated rash), reflux
>
> GU:  Right hydronephrosis and a non-visualized left kidney.
>
> Endo:  Hypocalcemia and PTH levels suggestive of hypoparathyroidism.
>
> Musculoskeletal: Segmentation abnormalities of thoracic spine are noted
> with associated scoliosis and rib abnormalities.  bilateral thumb
> abnormalities
>
> Genetics:  Microarray 29.9 Mb LOH in the short arm of chromosome #2.  This
> region was not deleted or duplicated.  Both copies at this region look
> similar.  One gene PHF9 is in this region and is associated with Fanconi
> anemia.  Given this information and some of his physical findings and the
> notion of Fanconi anemia was brought up.  We have attempted breakage
> studies twice, but did not have enough metaphases for breakage analysis.
> We are going to get skin fibroblasts and repeat breakage studies.  Notably
> he is not cytopenic or macrocytic.  Most of our Fanconi patients  have not
> had absent T cells.  We doubt Fanconi anemia, but are still evaluating.
>
> Immune evaluation:
>
> His newborn screen was positive for SCID.  No thymus noted on radiologic
> imaging.
> IgA < 7,  IgG 423, IgM 45,  IgE 21.8, no eosinophilia
> CD3 22 cells/uL, CD4 22 cells/uL, CD8 22 cells/uL, CD19 1738 cells/uL, NK
> 220 cells/uL
> CD4/CD45RA and CD8/CD45RA both < 20 cells/uL
> CD3/CD4/CD45RO and CD3/CD8/CD45RO both <20 cell/uL
> Mitogens all low (PHA, PWM, Con A).
> TCR Vb repertoire – some increased representation of families 14 and 17
> with concomitant decreases in other families.
> CD127/CD132 expression by flow – decreased expression overall on all
> lymphocytes (but patient is lymphopenic).  Normal expression on T cells
> (CD3 and CD3/4+), NK cells, and B cells.   Unlikely to be IL7R issue.
>
> We have a next gen sequencing panel pending for SCID (? Other forms of
> T-B+NK+ SCID) as well as genetic analysis for CHD7 given the possibility of
> “complete DiGeorge syndrome”.
>
> We are doing all of the standard precautions.  He is currently on
> isolation, no breast feeding, bactrim, IVIG, fluconazole, etc.
> Questions –
> 1) Does anyone have any other thoughts on what else should be done
> diagnostically?  We feel that his phenotype is more consistent with a
> complete DiGeorge syndrome.
> 2) We did HLA typing as well – difficult search with only 5/6 unrelated
> cords as a possibility at this point.   Is there any role for hematopoietic
> cell transplant?  If so, how would you prep?
> 3) Would consideration of a thymic transplant be a better approach for
> this patient?
> Thanks as always,
>
> Dave and Wan-yin
>
> David Buchbinder, MD
> Wan-yin Chan, MD
> CHOC Children's Hospital
>
> CHOCLX-MGSM made the following annotations
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> Wed Jan 14 2015 22:17:50
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